For the first time, researchers have corrected a disease-causing mutation in early stage human embryos with gene editing. The technique, which uses the CRISPR-Cas9 system, corrected the mutation for a heart condition at the earliest stage of embryonic development so that the defect would not be passed on to future generations.
With advances in stem cell technologies and gene editing, researchers are finally starting to address disease-causing mutations that impact potentially millions of people.
Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in otherwise healthy young athletes, and affects approximately 1 in 500 people overall. It is caused by a dominant mutation in the MYBPC3 gene, but often goes undetected until it is too late. Since people with a mutant copy of the MYBPC3 gene have a 50 percent chance of passing it on to their own children, being able to correct the mutation in embryos would prevent the disease not only in affected children, but also in their descendants.
Using IVF techniques, the researchers injected the best-performing gene-editing components into healthy donor eggs newly fertilized with the donor’s sperm. Then they analyzed all the cells in the early embryos at single-cell resolution to see how effectively the mutation was repaired.
The scientists were surprised by just how safe and efficient the method was. Not only did a high percentage of embryonic cells get repaired, but also gene correction didn’t induce any detectable off-target mutations and genome instability — major concerns for gene editing. In addition, the researchers developed a robust strategy to ensure the repair occurred consistently in all the cells of the embryo. (Spotty repairs can lead to some cells continuing to carry the mutation.)
Researchers emphasize that, although promising, these are very preliminary results and more research will need to be done to ensure no unintended effects occur.
Gene editing and future
Gene editing is still in its infancy so even though this preliminary effort was found to be safe and effective, it is crucial that researchers would continue to proceed with the utmost caution, paying the highest attention to ethical considerations.
The work is a collaboration between the Salk Institute, Oregon Health and Science University (OHSU) and Korea’s Institute for Basic Science and could pave the way for improved in vitro fertilization (IVF) outcomes as well as eventual cures for some of the thousands of diseases caused by mutations in single genes.
Source: Salk Institute for Biological Studies, US.